Development and comprehensive comparison of two on-line capillary electrophoretic methods for beta-secretase inhibitor screening

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F17%3A00095133" target="_blank" >RIV/00216224:14310/17:00095133 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1016/j.chroma.2017.08.065" target="_blank" >https://doi.org/10.1016/j.chroma.2017.08.065</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.chroma.2017.08.065" target="_blank" >10.1016/j.chroma.2017.08.065</a>

Result language

angličtina

Original language name

Development and comprehensive comparison of two on-line capillary electrophoretic methods for beta-secretase inhibitor screening

Original language description

Alzheimer’s disease is the most common cause of dementia, afflicting over 34 million patients worldwide. Since beta-secretase is a rate-limiting enzyme of the production of neurotoxic beta-amyloid peptide oligomers abnormally accumulated in the affected brain tissue, its specific inhibition appears to be a promising approach to slowing down or even stopping the progression of the disease. Hence two on-line capillary electrophoretic methods for studies of beta-secretase activity based on the principles of transverse diffusion of laminar flow profiles and electrophoretically mediated microanalysis were developed, both using a simple unlabeled peptide substrate and UV detection. The optimized procedures were thoroughly validated and applied for determining the enzyme’s kinetic parameters and the inhibition characteristics of two potent probe inhibitors. The resulting values were found to be comparable to literature data obtained with other analytical techniques. The suitability of the employed methodologies for different experimental designs is discussed on the basis of a statistical evaluation of the experimental data. The presented methods constitute a miniaturized and fully automated tool, which should be suitable for kinetic and inhibition studies of beta-secretase as a target for Alzheimer’s disease drug discovery in the early stages of the development of a new drug.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10600 - Biological sciences

Project

<a href="/en/project/GA16-06106S" target="_blank" >GA16-06106S: Capillary electrophoresis based high-throughput system for beta-secretase inhibitor screening as a therapeutic target of Alzheimer's disease</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Chromatography A

ISSN

0021-9673

e-ISSN

1873-3778

Volume of the periodical

1518

Issue of the periodical within the volume

October

Country of publishing house

CZ - CZECH REPUBLIC

Number of pages

8

Pages from-to

89-96

UT code for WoS article

000412621200010

EID of the result in the Scopus database

2-s2.0-85028615141